The research proposed in this application is ultimately aimed at the elucidation of the molecular events behind the insect-specific toxicity exhibited by certain subspecies of the gram positive spore-forming bacterium Bacillus thuringiensis. Preparations of B. thuringiensis spores and their associated crystal proteins have been effectively used for decades as environmentally-friendly biopesticides, and as more effective preparations are becoming commercially available, the use of "BT Toxin" will certainly grow. Due to safety considerations, cost effectiveness, and low environmental impact when compared to the standard pesticide alternatives, long range considerations of human and environmental health must take into account the natural alternatives to the highly toxic organo-phosphates currently in use. This lab reported the identification and cloning of a B. thuringiensis toxin receptor from the tobacco hornworm in 1993 and 1995, respectively; to date this receptor (BT-R1) remains the only insect toxin receptor cDNA to be cloned and functionally expressed in cell culture. The studies of BT-R1 and a second identified receptor included in this proposal are designed to lead to a better understanding of the dynamics of toxin/receptor interaction, and to conclusive studies of the physiology of intoxication. Such studies are vital if we are to understand and effectively counter the development of resistance likely to gradually appear in insect populations as the toxins gain widespread acceptance.